Flashcards in CHAPTER 11: EXOCRINE PANCREAS, GALLBLADDER, & LIVER PATHOLOGY Deck (190):
What is jaundice?
Yellow discoloration of the skin
What is the earliest sign of jaundice?
Classically, how high does the bilirubin need to be for the manifestation of jaundice?
Greater than 2.5 mg/dL
When the lifespan of a RBC is up, where are they degraded?
Macrophages of the "Reticuloendothelial System" i.e. splenic macrophages
Describe bilirubin metabolism starting with the splenic macrophage.
1) Hb is broken down into Heme + Globin
- Globin is broken down into amino acids that are recycled
- Heme is separated into Iron (recycled) and Protoprophyrin
2) Protoporphyrin is converted into unconjugated bilirubin (UCB)
3) UCB binds albumin and is taken to the liver
4) Liver UGT conjugates UCB to CB
5) CB is released into bile canaliculi to form bile
6) Bile is transported in the bile ducts to the Gallbladder where it is stored
7) On stimulation, bile is release into duodenum
What happens to CB that reaches the duodenum?
1) Intestinal flora convert bile into Urobilinogen
2) Urobilinogen is oxidized to:
What makes the stool brown?
Sterocobilin, an oxidation product of Urobilinogen
What makes the urine yellow?
What enzyme conjugates bilirubin in the hepatocyte?
Uridine glucuronyl transferase (UGT)
Describe the etiology of hyperbilirubinemia in extravascular hemolysis or ineffective erythropoiesis.
- Extravascular hemolysis= breakdown of RBCs that are taken up by splenic macrophages
- Ineffective erythropoiesis= death of RBC in bone marrow leading to consumption by macrophages in the bone marrow
BOTH result in high levels of UCB that overwhelm the conjugating ability of the liver
What lab finding is seen in extravascular hemolysis or ineffective erythropoieses?
What are the clinical features of extravascular hemolysis or ineffective erythropoiesis?
*UCB is not water soluble an is absent from urine; eventally it will be conjugated leading to:
1) Dark urine due to increased UROBILINOGEN
2) Increased risk for bilirubin gallstones b/c of increased bilirubin
Describe the etiology of hyperbilirubinemia in physiologic jaundice of the newborn.
Newborn liver has transiently low UGT
What lab finding is seen in physiologic jaundice of the newborn.
What are the clinical manifestations of hyperbilirubinemia in physiologic jaundice of the newborn?
UCB is fat soluble and deposits in the brain, leading to Kernicterus
What is the treatment for physiologic jaundice of the newborn?
What is the effect of phototherapy in physiologic jaundice of the newborn?
This treatment makes UCB water soluble
*It does NOT conjugate UCB*
Describe the etiology of hyperbilirubinemia in Gilbert Syndrome.
Autosomal recessive defect in UGT that decreases conjugating ability of the liver
What lab finding is seen in Gilbert Syndrome?
What are the clinical manifestations of Gilbert Syndrome?
- Mostly asymptomatic
- Jaundice during stress
Describe the etiology of hyperbilirubinemia in Crigler-Najjar Syndrome.
Autosomal recessive ABSENCE of UGT
What is the lab finding in Crigler-Najjar Syndrome?
Dramatically elevated UCB
What are the clinical manifestations of Crigler-Najjar Syndrome?
Kernicterus that is usually fatal
Describe the etiology of hyperbilirubinemia in Dubin-Johnson Syndrome?
Autosomal recessive deficiency of bilirubin transport protein (MDR-2); CB does not get into the bile canaliculi
What lab finding is associated with Dubin-Johnson Syndrome?
What are the clinical manifestations of Dubin-Johnson Syndrome?
- DARK LIVER
What is Rotor Syndrome?
Similar to Dubin-Johnson, but liver is NOT dark
Describe the etiology of hyperbilirubinemia in biliary tract obstruction?
Bilary tract is blocked--whatever is in the bile leaks out into the blood
List the most common causes if biliary tract obstruction.
2) Pancreatic carcinoma
5) Liver fluke
Cholangiocarcinoma is a cancer of the biliary tract epithelium
What lab findings are seen in biliary tract obstruction?
1) Elevated CB
2) Decreased urine urobilinogen
3) Increased ALP
What are the clinical manifestations of biliary tract obstruction?
1) Bile acids/salts leak into the skin causing PRURITUS
2) Cholesterol leaks into the blood from bile causing HYPERCHOLESTEROLEMIA and XANTHOMAS
3) No bile in bowel causes PALE STOOL, MALABSORPTION, STEATORRHEA
4) CB is water souble causing BILIRUBINURIA
Describe the etiology of hyperbilirubinemia in viral hepatitis.
Inflammation (virus-induced) disrupts hepatocytes and small bile ductules
What are the lab findings seen in viral hepatitis?
Increased CB and UCB
What are the clinical manifestations of viral hepatitis?
1) Dark urine due to bilirubinuria (CB)
2) Normal or decreased urine urobilinogen
What is viral hepatitis?
Virus induced inflammation of the liver parenchyma
What three viruses can cause viral hepatitis?
1) Hepatitis virus
How do patients with acute hepatitis present?
- Dark urine (CB is water soluble and filtered into urine)
What type of hyperbilirubinemia cause the jaundice seen in acute hepatitis?
Mixed CB and UCB
- CB= due to bile ductule destruction
- UCB= hepatocyte destruction
What are the lab markers associated with acute viral hepatitis?
Elevated liver enzymes i.e. ALT and AST (ALT higher)
What mediates the inflammation of hepatocytes seen in acute viral hepatitis?
How is chronic hepatitis defined?
Symptoms and elevated liver enzymes for greater than 6 months
Where is the inflammation seen in acute hepatitis?
- Lobules of the liver, between hepatocytes
- Portal tracts
Where is the inflammation seen in chronic hepatitis?
Predominantly in the portal tract ALONE (vs. acute in liver lobules)
How are Hepatitis A and E transmitted?
What is Hepatitis A transmission associated with?
What is Hepatitis E transmission associated with?
- Contaminated water
- Undercooked seafood
When is HEV infection worrisome? Why?
Pregnant women b/c it can cause fulminant hepatitis
What is the serologic marker of active HAV or HEV infection?
Anti-HAV or Anti-HEV IgM antibodies
What is the serologic marker of previous HAV or HEV infection?
Anti-HAV or Anti-HEV IgG antibodies
What antibody indicates prior immunization to HAV?
Anti-HAV IgG antibodies
Do HAV and HEV cause acute or chronic hepatitis?
How is HBV transmitted?
How often does HBV infection result in chronic hepatitis?
Only 20% of the time
What is the serologic marker for the acute phase of HBV infection?
What indicates progression of HBV infection from acute to chronic?
HBsAG for more than 6 months
What is the serologic marker for "acute battle" against HBV infection?
HBcAB (core antibody) IgM
What is the serologic marker for the window period in HBV infection?
What are the serologic markers for resolved HBV infection?
1) HBsAB IgG*
2) HBcAB IgG
*Marks "victory" against HBV infection
What is the serologic marker for HBV immunization?
What is the serologic marker for HBV infectivity?
HBeAg (HBV envelope antigen) and/or HBV DNA
What is the route of transmission for HCV infection?
Parenteral, but highly associated with bad behavior i.e.
- Unprotected sex
- Needle stick
What type of infection often result from HCV?
Acute hepatitis that progresses to chronic
What is the key serologic marker for HCV?
How do you know if a patient has resolving HCV infection or has progressed to chronic?
- Decreased levels= recovery
- Persistence= chronic disease
What does HDV require for infection?
What are the two type of HDV infection?
1) Superinfection= HBV first, then HDV*
2) Coinfection= both infect at same time
*This is WORSE*
What is cirrhosis?
End stage liver disease
What are the pathologic characteristics of cirrhosis?
Disruption of the normal hepatic parenchyma with:
1) Bands of fibrosis
2) Regenerative nodules of hepatocytes
What cell mediates the fibrosis seen in cirrhosis?
What do the Stellate cells secrete that causes cirrhosis?
List the clinical signs of cirrhosis. What are the major categories of symptoms? What specific signs and symptoms fall into each category?
1) Portal HTN leading to:
- Congestive splenomegaly (consumes RBCs/platelets)
- Portosystemic shunts
- Hepatorenal syndrome
2) Decreased detoxificiaton
- Hyperammonemia-->AMS, asterixis, coma
- Hyperestrogen-->gynecomastia, spider angiomata, palmar erythema
3) Decreased protein synthesis
- Hypoalbuminemia (edema)
What is the Hepatorenal Syndrome?
Rapid kidney failure in the face of portal HTN
What test is used to follow the degree of coagulopathy in the setting of cirrhosis?
PT (Prothrombin Time)
What is Alcohol-Related Liver Disease?
Damage of the hepatic parenchyma due to consumption of alcohol
What are the three presentations of Alcohol-Related Liver Disease?
1) Fatty Liver
2) Alcoholic Hepatitis
What are the features of Fatty Liver?
Accumulation of fat in hepatocytes resulting in:
- Heavy/ greasy liver
- RESOLVES with abstinence
What is Alcoholic Hepatitis?
Chemical injury to hepatocytes from alcohol--seen with BINGE drinking
What metabolite mediates the liver damage seen in alcoholic hepatitis?
What microscopic finding is pathognomonic for alcoholic hepatitis?
"Mallory bodies" alcohol damaged intermediate filaments in the hepatocytes
How does alcoholic hepatitis present?
1) Painful hepatomegaly
2) Elevated liver enzymes
*****AST GREATER THAN ALT*****
Why is AST significantly elevated in alcoholic hepatits?
- Alcohol preferentially damages the mitochondria
- AST is located in the mitochondria
- Damage result in AST leaking from the mitochondria/ hepatocyte into the serum
What is the complication of chronic alcoholic liver disease?
What is Non-alcoholic Fatty Liver Disease (NAFLD)?
Fatty change, hepatitis, or cirrhosis that develops WITHOUT KNOWN INSULT
*Associated with obesity
In terms of labs, how do you tell the difference between alcoholic liver disease and NAFLD?
ALT is greater than AST in NAFLD
What is hemochromatosis?
Excess body iron that deposits in tissue and damages organs, including the liver
Describe the development of organ damage seen in hemochromatosis?
- Excess iron undergoes the Fenton Reaction to generate free radical
- Free radicals mediate damage to organs
What is the difference between Primary and Secondary Hemochromatosis?
First, recall that enterocytes regulate the ABSORPTION of iron
Primary= defect in this regulation causes iron to constantly be absorbed via the gut
- HFE gene mutation
Secondary= complication of blood transfusion
When does Hemochromatosis usually present?
Late adulthood b/c it takes a while for enough iron to build-up in the body to cause symptoms
What are the symptoms of Hemochromatosis?
2) Secondary DM
3) Bronze skin
+ Cardiac arrhythmia and gonadal dysfunction
What labs are seen in Hemochromatosis?
- High Ferretin
- Low TIBC
- High Serum Iron
- High % saturation
How is Hemochromatosis diagnosed?
Biopsy--brown pigment seen in hepatocytes
How is Hemochromatosis differentiated from Lipofuscin?
Prussian Blue Stain
(Iron turns blue, Lipofuscin does NOT--remember this is the "old age" pigment in cells)
How is Hemochromatosis treated?
What are patients with Hemochromatosis at an increased risk for?
What is Wilson's Disease?
Disease characterized by increased copper accumulation in the body
What genetic defect is seen in Wilson's Disease?
Autosomal recessive mutation in ATP7B--codes for COPPER TRANSPORTER
****This defect prevents the transport of copper from the liver into the bile*****
What transports copper in the body?
How does copper mediate organ damage?
Like iron, undergoes Fenton reaction to generate free radicals
How does Wilson's Disease typically present?
2) Neuropsychiatric manifestations
3) Kayser-Fleisher rings in cornea
What are patients with Wilson's Disease at increased risk for?
How is Wilson's Disease treated?
D-penicillamine, which is a CHELATING AGENT
What labs are specific for Wilson's Disease?
1) Increased urinary copper
2) Decreased serum ceruloplasmin
3) Increased copper on liver biopsy
What is Primary Biliary Cirrhosis (PBC)?
Autoimmune granulomatous destruction of INTRAHEPATIC BILE DUCTS
What patient population is PBC classically seen in?
Middle aged women (40 y/o)
What antibody is associated with PBC?
Anti-mitochondrial antibody (AMA)
How do patients with PBC present?
1) Obstructive jaundice
What is Primary Sclerosing Cholangitis (PSC)?
Disorder leading to inflammation and fibrosis of the INTRAHEPATIC AND EXTRAHEPATIC bile ducts
What is the classic appearance of periductal fibrosis on microscopy seen in PSC?
How does PSC classically appear on imaging?
"Beads on a string"
What disease is PSC highly associated with?
Ulcerative colitis (IBD)
What antibody is highly associated with PSC?
What is the classic presentation of PSC?
Obstructive jaundice that leads to cirrhosis
What cancer are patients with PSC at an increased risk for?
Cholangiocarcinoma--cancer of the bile ducts
What is Reye Syndrome?
Fulminant liver failure and encephalopathy
*****SEEN IN CHILDREN WITH VIRAL ILLNESS THAT TAKE ASPIRIN*****
How do kids with Reye Syndrome present?
- Elevated liver enzymes
- Nausea and vomiting
*****Can progress to COMA AND DEATH*****
What is the one disease where you give a child with what resembles a viral illness aspirin?
Kawasaki Disease--inflammation of the medium sized vessels including the coronary vessels
What is a Hepatic Adenoma?
Benign glandular tumor of hepatocytes
What are Hepatic Adenmoas commonly associated with?
*****Note that these will regress with the cessation of oral contraceptives****
What is the most feared complication of Hepatic Adenomas?
Rupture during pregnancy
*****High levels of estrogen increase the risk of rupture during pregnancy--ruptures through the liver capsule and causes intraperitoneal hemorrhage*****
List the risk factors for Hepatocellular Carcinoma (HCC).
1) Chronic hepatitis e.g. HBV or HCV induced
2) Anything causing cirrhosis:
- Alcoholic liver disease
- Wilson's Disease
- Alpha-1 antitrypsin disease
3) Aflatoxins from Aspergillus
What is the mechanism of HCC development from Aflatoxins?
Aflatoxins induce p53 mutations
What is Budd-Chiari Syndrome?
Thrombosis of the hepatic vein i.e. vein leading from the liver to the IVC
How does Budd-Chiari Syndrome present?
Painful heptosplenomegaly and ascites
Why does HCC increase the risk for Budd-Chiari Syndrome?
HCC tends to invade the hepatic vein, increasing the risk for thrombosis
Why is there a poor prognosis associated with HCC?
*****Patients with HCC commonly already have another liver condition that masks the symptoms of HCC until the disease is very far along*****
What is the serum tumor marker that is highly associated with HCC?
What is the most common source of liver tumors?
METASTASES i.e. tumors that have mets to the liver are more common that primary liver tumors
What are the common sources of mets to the liver?
How do mets to the liver present?
- Nodular liver
*****Results in a free liver edge i.e. an edge of the liver that can be palpated, with nodules that can be felt on physical exam*****
What is an annular pancreas?
Developmental defect where the pancreas forms as a ring around the duodenum, increasing the risk of duodenal obstruction
What is acute pancreatitis?
Inflammation and hemorrhage of the pancreas caused by premature activation of pancreatic digestive enzymes
What pancreatic enzyme is first activated in acute pancreatitis?
What type of necrosis is seen in acute pancreatitis?
1) Liquefactive necrosis of the pancreas
2) Fat necrosis of peripancreatic fat
What are two most common causes of pancreatitis?
How does alcoholism cause pancreatitis?
- Alcohol causes contraction of the Sphincter of Oddi
- Sphincter of Oddi is the opening of the exocrine pancreas into the duodenum
What type of trauma can cause pancreatitis?
What is the specific mechanism of trauma that can often result in pancreatitis?
MVA with the seat belt worn over the abdomen
List the less common causes of acute pancreatitis.
2) Hypercalcemia and hyperlipidemia
4) Scorpion stings
6) Rupture of a posterior duodenal ulcer
How do patients present with acute pancreatitis?
- Epigastric abdominal pain that radiates to the back
- Nausea and vomiting
- Periumbilical and flank hemorrhage
*Note that the last two are referred to as Cullen's and Gray-Turner's Signs*
What serum enzyme elevation is specific to pancreatitis?
Why is hypocalcemia seen in pancreatitis?
Necrosis of the peripancreatic fat and soponification consumes Ca++
What is hypocalcemia in the face of acute pancreatitis an indication of?
What are the complications of acute pancreatitis?
2) Pancreatic pseudocyst
3) Pancreatic abscess
4) DIC and ARDS
What lab is associated with a pancreatic pseudocyst?
Persistently elevated amylase
What causes chronic pancreatitis?
Recurrent acute pancreatitis
What is chronic pancreatitis?
Fibrosis of the pancreatic parenchyma secondary to recurrent pancreatitis
What causes chronic pancreatitis in adults?
What causes chronic pancreatitis in children?
What are the clinical features of chronic pancreatitis?
- Epigastric abdominal pain radiating to the back
- Pancreatic insufficiency
- Dystrophic calcification of the pancreas
- Secondary DM
What are the symptoms of pancreatic insufficiency?
- Fat soluble vitamin deficiency
What cancer are patients with chronic pancreatitis at an increased risk for?
What is pancreatic carcinoma?
Adenocarcinoma (glandular) neoplasia arising from the pancreatic ducts (vs. acini)
What are the major risk factors for pancreatic carcinoma?
2) Chronic pancreatitis
How do patients with pancreatic carcinoma present?
- Epigastric abdominal pain
- Weight loss
How does pancreatic carcinoma present when it arises in the head of the pancreas?
Signs of obstructive jaundice and:
- Pale stool
- Palpable gallbladder
*Blocks the flow of bile*
If you see a thin elderly female that suddenly develops DM, what do you need to be concerned about?
Pancreatic carcinoma obstructing the endocrine pancreas causing secondary DM
What is the serum tumor marker for pancreatic carcinoma?
How is pancreatic carcinoma treated?
What is biliary atresia?
Congenital failure to form the lumen of the extrahepatic biliary tree leading to obstruction in the first 3x months of life
What are the symptoms of biliary atresia?
- CB jaundice
What does cholelithiasis refer to?
What causes cholelithiasis?
Precipitation of cholesterol or bilirubin in the bile
What causes the precipitation of cholesterol or bilirubin in the bile, forming gallstones?
1) Supersaturation i.e. high concentrations of either of the above
2) Decreased phospholipids or bile acids
*Phospholipids e.g. lecithin/ bile acids make cholesterol and bilirubin more soluble
What is an important side effect of Cholestyramine?
- This is a bile acid binding resin
- Prevents recycling of bile acids, causing increased production (cholesterol dependent) eventually lowering cholesterol
Less bile acids make cholesterol less soluble as well, leading to cholesterol stone formation
What is the most common type of stone in the west?
Are cholesterol stones radiolucent or radiopaque?
Radiolucent i.e. don't show up on radiograph unless there is calcification
What are the risk factors for cholesterol gallstones?
2) Estrogen i.e. female gender
4) Native American
5) Crohn Disease
What is the MOA of Clofibrate?
This drug INCREASES the activity of HMG-COA reductase (increased cholesterol)
How do bilirubin stones differ from cholesterol gallstones?
Bilirubin stones are radio-opaque
What are the risk factors for bilirubin stones?
1) Extravascular hemolysis (supersaturation)
2) Biliary tract infection
What is biliary colic?
Waxing and waning RUQ pain
What causes biliary colic?
Gallbladder contracting against gallstone lodged in cystic duct
What is acute cholecystitis?
Acute inflammation of the gallbladder wall
What causes acute cholecystitis?
- Gallstone in cystic duct
- Increased pressure in gallbladder squeezes off blood supply-->ischemia
Ischemia leads to bacterial overgrowth
How does acute cholecystitis present?
- RUQ pain radiating to the RIGHT SCAPULA
- Nausea/ vomiting
What labs are associated with acute cholecystitis?
- Elevated WBC count
- Increased serum alkaline phosphatase (ALP)
What is chronic cholecystitis?
Chronic gallbladder inflammation caused by longstanding cholelitheiasis
What is a histologic hallmark of chronic cholecystitis?
Rokitansky-Aschoff sinus formation
*Gallbladder mucosa that dives into the smooth muscle of the gallbladder*
How do patients with chronic cholecystitis present?
- Vague RUQ pain
- Worse after eating
What is a complication of chronic cholecystitis?
Porcelain gallbladder i.e. dystrophic calcification of the gallbladder
What is treatment for chronic cholecystitis?
What is ascending cholangitis?
Bacterial infection of the bile ducts
What typically causes ascending cholangitis?
"Ascending" infection of enteric gram negative bacteria
How does ascending cholangitis present?
- RUQ abdominal pain
What is ascending cholangitis assocaited with?
Choledocholithiasis i.e. gallstone in the bile duct, preventing the normal "washing away" of bacteria
What is a gallstone ileus?
Gallstone that obstructs the small intestine
How does a gallstone ileus form?
Fistula between the gallbladder and small bowel
What type of cancer is gallbladder carcinoma?
What is the major risk factor for gallbladder carcinoma?
Gallstones especially with porcelain gallbladder